Zosuquidar, daunorubicin, and cytarabine for the treatment of cancer

Abstract

The present invention relates to a method of treating patients with solid tumors, leukemias, and other malignancies using a combination of zosuquidar, daunorubicin, and cytarabine. The invention is also directed to pharmaceutical formulations comprising zosuquidar, daunorubicin, and cytarabine. The formulations are particularly effective in treating relapsed Acute Myelogenous Leukemia (AML).

1 . A method of treating a malignancy in a patient, the method comprising the steps of: 
 conducting a diagnostic test, whereby it is determined that the malignancy expresses or selects P-glycoprotein or exhibits positive efflux pump activity; and    administering zosuquidar and a chemotherapeutic agent that is a substrate for P-glycoprotein to the patient.    
   
   
       2 . The method of  claim 1 , wherein the malignancy is acute myelogenous leukemia.  
   
   
       3 . The method of  claim 1 , wherein the malignancy is a carcinoma.  
   
   
       4 . The method of  claim 3 , wherein the carcinoma is breast cancer.  
   
   
       5 . The method of  claim 3 , wherein the carcinoma is ovarian cancer.  
   
   
       6 . The method of  claim 1 , wherein the malignancy is a sarcoma.  
   
   
       7 . The method of  claim 1 , wherein the malignancy is a hematologic malignancy.  
   
   
       8 . The method of  claim 7 , wherein the hematologic malignancy is selected from the group consisting of acute lymphoblastic leukemia, chronic myeloid leukemia, plasma cell dyscrasias, lymphoma, and myelodysplasia.  
   
   
       9 . The method of  claim 1 , wherein the chemotherapeutic agent is an anthracycline.  
   
   
       10 . The method of  claim 9 , wherein the anthracycline is selected from the group consisting of doxorubicin, daunorubicin, epirubicin, idarubicin, and mitoxantrone.  
   
   
       11 . The method of  claim 1 , wherein the chemotherapeutic agent is a Topoisomerase-II inhibitor.  
   
   
       12 . The method of  claim 1 , wherein the Topoisomerase-II inhibitor is etoposide or teniposide.  
   
   
       13 . The method of  claim 1;  wherein the chemotherapeutic agent is a vinca.  
   
   
       14 . The method of  claim 13 , wherein the vinca is selected from the group consisting of vincristine, vinblastine, vinorelbine, and vindesine.  
   
   
       15 . The method of  claim 1 , wherein the chemotherapeutic agent is a taxane.  
   
   
       16 . The method of  claim 15 , wherein the taxane is paclitaxel or docetaxel.  
   
   
       17 . The method of  claim 1 , wherein the chemotherapeutic agent is Gleevec.  
   
   
       18 . The method of  claim 1 , wherein the chemotherapeutic agent is dactinomycin.  
   
   
       19 . The method of  claim 1 , wherein the chemotherapeutic agent is mitomycin.  
   
   
       20 . The method of  claim 1 , wherein the chemotherapeutic agent is mithramycin.  
   
   
       21 . The method of  claim 1 , wherein the chemotherapeutic agent is Mylotarg.